Novel heteroaryl derivatives and their use as medicaments

ABSTRACT

The invention relates to novel quinoline derivatives of the formula 1, to their preparation and to their use as medicaments, in particular for treating tumors.

FIELD OF THE INVENTION

[0001] The invention relates to novel heteroaryl derivatives of theformula 1, to their preparation and to their use as medicaments, inparticular for treating tumors.

DESCRIPTION OF THE INVENTION

[0002] According to one aspect of the invention, novel quinolinederivatives of the formula 1

[0003] in which

[0004] R, R₁, R₂, R₃ can be attached to any of the quinoline carbonatoms C₂ to C₈, are the same or different and independently of oneanother denote hydrogen, straight-chain or branched (C₁-C₈)-alkyl,(C₃-C₇)-cycloalkyl, straight-chain or branched (C₁-C₈)-alkylcarbonyl,preferably acetyl, straight-chain or branched (C₁-C₈)-alkoxy, halogen,aryl-(C₁-C₈)-alkoxy, preferably benzyloxy or phenylethyloxy, nitro,amino, mono-(C₁-C₄)-alkylamino, di-(C₁-C₄)-alkylamino,(C₁-C₈)-alkoxycarbonylamino, (C₁-C₆)-alkoxycarbonylamino-(C₁-C₈)-alkyl,cyano, straight-chain or branched cyano-(C₁-C₆)-alkyl, carboxyl,(C₁-C₈)-alkoxycarbonyl, (C₁-C₄)-alkyl which is substituted by one ormore fluorine atoms, preferably the trifluoromethyl group,carboxy-(C₁-C₈)-alkyl or (C₁-C₈)-alkoxycarbonyl-(C₁-C₆)-alkyl,(C₂-C₆)-alkenyl, preferably allyl, (C₂-C₆)-alkynyl, preferably ethynylor propargyl, straight-chain or branched cyano-(C₁-C₆)-alkyl, preferablycyanomethyl, aryl, where the aryl radical can be unsubstituted or mono-or polysubstituted by the same or different substituents from the groupof halogen, straight-chain or branched (C₁-C₈)-alkyl,(C₃-C₇)-cycloalkyl, carboxyl, straight-chain or branched(C₁-C₈)-alkoxycarbonyl, preferably tert-butoxycarbonyl, bytrifluoromethyl, hydroxyl, straight-chain or branched (C₁-C₈)-alkoxy,preferably methoxy or ethoxy, benzyloxy, nitro, amino,mono-(C₁-C₄)-alkylamino, di-(C₁-C₄)-alkylamino, cyano, straight-chain orbranched cyano-(C₁-C₆)-alkyl, where additionally R and R₁ or R₂ and R₃may form a fused aromatic 6-membered ring with the quinoline ringforming an acridine ring which for its part can be substituted at any Catom ring position by the radicals R, R₁, R₂ and R3 having the meaningsmentioned above;

[0005] Z is oxygen or sulfur, where the radical

[0006]  substituted on the quinoline heterocycle can be attached to Catoms C₂-C₈ of the quinoline ring skeleton;

[0007] P, Q independently of one another represent oxygen or in eachcase two hydrogen atoms (i.e. —CH₂—);

[0008] X is nitrogen or C—R₅, where R₅ represents hydrogen or(C₁-C₆)alkyl;

[0009] n,m independently of one another denotes an integer between 0-3,with the proviso that in the case n=0, X denotes a CR₅R₆ group where R₅and R₆ independently of one another represent hydrogen or (C₁-C₆)-alkyland that the nitrogen atom adjacent to the C═Z group is substituted by ahydrogen atom or a (C-C₆)-alkyl group;

[0010] R₄ or a straight-chain or branched (C₁-C₂₀)-alkyl radical whichcan be saturated or unsaturated, with one to three double and/or triplebonds, and which can be unsubstituted or may optionally be substitutedat the same or different C atoms by one, two or more aryl, heteroaryl,halogen, cyano, (C₁-C₆)-alkoxycarbonylamino, (C₁-C₆)-alkoxy, amino,mono-(C₁-C₄)-alkylamino or di-(C₁-C₄)-alkylamino; a (C₆-C₁₄)-arylradical, (C₆-C₁₄)-aryl-(C₁-C₄)-alkyl radical, or a a (C₂-C₁₀)-heteroarylor (C₂-C₁₀)-heteroaryl-(C₁-C₄)-alkyl radical which contains one or moreheteroatoms selected from the group of N, O and S, where the(C₁-C₄)-alkyl radical can be unsubstituted or mono- or polysubstitutedby the same or different substituents from the group of (C₁-C₆)-alkyl,halogen or oxo (═O), and where the (C₆-C₁₄)-aryl or (C₂-C₁₀)-heteroarylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of straight-chain or branched(C₁-C₈)-alkyl, (C₃-C₇)-cycloalkyl, halogen, cyano,(C₁-C₆)-alkoxycarbonylamino, (C₁-C₆)-alkoxy, carboxyl,(C₁-C₈)-alkoxycarbonyl, straight-chain or branched (C₁-C₆)-alkyl whichis substituted by one or more fluorine atoms, preferablytrifluoromethyl, hydroxyl, straight-chain or branched (C₁-C₈)-alkoxy,preferably methoxy or ethoxy, where adjacent oxygen atoms may also belinked by (C₁-C₂)-alkylene groups, preferably by a methylene group,benzyloxy, nitro, amino, mono-(C₁-C₄)-alkylamino, di-(C₁-C₄)-alkylamino,aryl, which for its part can be unsubstituted or mono- orpolysubstituted by the same or different substituents from the group ofstraight-chain or branched (C₁-C₈)-alkyl, (C₃-C₇)-cycloalkyl, carboxyl,straight-chain or branched (C₁-C₈)-alkoxycarbonyl, by trifluoromethyl,hydroxyl, straight-chain or branched (C₁-C₈)-alkoxy, preferably methoxyor ethoxy, benzyloxy, nitro, amino, mono-(C₁-C₄)-alkylamino,di-(C₁-C₄)-alkylamino, cyano, straight-chain or branchedcyano-(C₁-C₆)-alkyl;

[0011] and their structural isomers and stereoisomers, in particulartautomers, diastereomers and enantiomers, and their pharmaceuticallyacceptable salts, in particular acid addition salts, are provided.

[0012] Thus, for example, the compounds of the formula (1) according tothe invention which have one or more centers of chirality and which arepresent as racemates can be separated by methods known per se into theiroptical isomers, i.e. enantiomers or diastereomers. The separation canbe carried out by column separation on chiral phases or byrecrystallization from an optically active solvent or using an opticallyactive acid or base or by derivatization with an optically activereagent, such as, for example, an optically active alcohol, andsubsequent removal of the radical.

[0013] Furthermore, the quinoline derivatives of the formula (1)according to the invention can be converted into their salts withinorganic or organic acids, in particular, for pharmaceutical use, intotheir physiologically acceptable salts. Acids which are suitable forthis purpose are, for example, hydrochloric acid, hydrobromic acid,sulfuric acid, phosphoric acid, fumaric acid, succinic acid, lacticacid, citric acid, acetic acid, tartaric acid, malic acid, embonic acid,malonic acid, trifluoroacetic acid or maleic acid.

[0014] Moreover, the compounds of the formula (1) according to theinvention can, if they contain a sufficiently acidic group, such as acarboxyl group, be converted, if desired, into their salts withinorganic or organic bases, in particular, for pharmaceutical use, intotheir physiologically acceptable salts. Bases which are suitable forthis purpose are, for example, sodium hydroxide, potassium hydroxide,calcium hydroxide, lysine, cyclohexylamine, ethanolamine, diethanolamineand triethanolamine.

[0015] According to a preferred embodiment, quinoline derivatives of theformula 1 are provided in which R, R1, R2, R3, X, Z, P, Q, n and m havethe meanings given above and

[0016] R₄ denotes a straight-chain or branched (C₁-C₂₀)-alkyl radicalwhich can be saturated or unsaturated, with one to three double and/ortriple bonds, and which can be unsubstituted or optionally substitutedon the same or different C atoms by one, two or more aryl, heteroaryl,halogen, (C1-C6)-alkoxy, amino, mono-(C₁-C₄)-alkylamino ordi-(C₁-C₄)-alkylamino;

[0017] a phenyl ring or a naphthyl ring, each of which can beunsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of straight-chain or branched (C₁-C₈)-alkyl,(C₃-C₇)-cycloalkyl, halogen, carboxyl, (C₁-C₈)-alkoxycarbonyl,straight-chain or branched (C₁-C₆)-alkyl which is substituted by one ormore fluorine atoms, preferably trifluoromethyl, hydroxyl,straight-chain or branched (C₁-C₈)-alkoxy, preferably methoxy or ethoxy,where adjacent oxygen atoms may also be linked by (C₁-C₂)-alkylenegroups, preferably a methylene group, benzyloxy, nitro, amino,mono-(C₁-C₄)-alkylamino, di-(C₁-C₄)-alkylamino, aryl, which for its partcan be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of straight-chain or branched(C₁-C₈)-alkyl, (C₃-C₇)-cycloalkyl, carboxyl, straight-chain or branched(C₁-C₈)-alkoxycarbonyl, by trifluoromethyl, hydroxyl, straight-chain orbranched (C₁-C₈)-alkoxy, preferably methoxy or ethoxy, benzyloxy, nitro,amino, mono-(C₁-C₄)-alkylamino, di-(C₁-C₄)-alkylamino, cyano,straight-chain or branched cyano-(C₁-C₆)-alkyl;

[0018] a 2-, 4-, 5- or 6-pyrimidinyl radical, or a 2-, 4-, 5- or6-pyrimidinyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkyl radical canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 2-, 4-, 5- or 6-pyrimidinyl radical can be unsubstituted or mono- totrisubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0019] a 3-, 4-, 5- or 6-pyridazinyl radical, or a 3-, 4-, 5- or6-pyridazinyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkyl radical canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 3-, 4-, 5- or 6-pyridazinyl radical can be unsubstituted or mono- totrisubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0020] a 2-, 3-, 5- or 6-pyrazinyl radical, or a 2-, 3-, 5- or6-pyrazinyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkyl radical canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 2-, 3-, 5- or 6-pyrazinyl radical can be unsubstituted or mono- totrisubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0021] a 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl radical, or a 3-, 4-, 5-,6-, 7-, or 8-cinnolinyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl radical can beunsubstituted or mono- to pentasubstituted by the same or differentsubstituents from the group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro,amino, mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0022] a 2-, 4-, 5-, 6-, 7-, or 8-quinazolinyl radical, or a 2-, 4-, 5-,6-, 7-, or 8-quinazolinyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of hydrogen, (C₁-C₆)-alkyl,halogen or oxo (═O), and the or [sic] 2-, 4-, 5-, 6-, 7-, or8-quinazolinyl radical can be unsubstituted or mono- to pentasubstitutedby the same or different substituents from the group of hydrogen,(C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0023] a 2-, 3-, 5-, 6-, 7-, or 8-quinoxalinyl radical, or a 2-, 3-, 5-,6-, 7-, or 8-quinoxalinyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the or [sic] 2-, 3-, 5-, 6-, 7-, or 8-quinoxalinyl radical canbe unsubstituted or mono- to pentasubstituted by the same or differentsubstituents from the group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro,amino, mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0024] a 1-, 4-, 5-, 6-, 7-, or 8-phthalazinyl radical, or a 1-, 4-, 5-,6-, 7-, or 8-phthalazinyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the or [sic] 1-, 4-, 5-, 6-, 7-, or 8-phthalazinyl radical canbe unsubstituted or mono- to pentasubstituted by the same or differentsubstituents from the group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro,amino, mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0025] a 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl radical, or a 2-, 3-, 4-,5-, 6-, 7 or 8-quinolyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl radical can beunsubstituted or mono- to hexasubstituted by the same or differentsubstituents from the group of hydrogen, (C₁-C₆)-alkyl, preferablymethyl, particularly preferably 2-methyl, halogen, nitro, amino,mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0026] a 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl radical, or a 1-, 3-,4-, 5-, 6-, 7- or 8-isoquinolyl-(C₁-C₄)-alkyl radical, where the(C₁-C₄)-alkyl radical can be unsubstituted or mono- or polysubstitutedby the same or different substituents from the group of (C₁-C₆)-alkyl,halogen or oxo (═O), and the 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolylradical can be unsubstituted or mono- to hexasubstituted by the same ordifferent substituents from the group of hydrogen, (C₁-C₆)-alkyl,halogen, nitro, amino, mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino,hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0027] a 2-, 6-, 8- or 9-[9H]-purinyl radical, or a 2-, 6-, 8- or9-[9H]-purinyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkyl radicalcan be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 2-, 6-, 8- or 9-[9H]-purinyl radical can be unsubstitutedor mono- to trisubstituted by the same or different substituents fromthe group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino,mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0028] a 2-, 6-, 7- or 8-[7H]-purinyl radical, or a 2-, 6-, 7- or8-[7H]-purinyl-(C₁-C₄)-alkyl radical, where the (C₁-C₄)-alkyl radicalcan be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 2-, 6-, 7- or 8-[7H]-purinyl radical can be unsubstitutedor mono- to trisubstituted by the same or different substituents fromthe group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino,mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0029] a 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl radical, or a 1-,2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl-(C₁-C₄)-alkyl radical, wherethe (C₁-C6)-alkyl radical can be unsubstituted or mono- orpolysubstituted by the same or different substituents from the group of(C₁-C₆)-alkyl, halogen or oxo (═O), and the 1-, 2-, 3-, 4-, 5-, 6-, 7-,8- or 9-acridinyl radical can be unsubstituted or mono- tooctasubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0030] a 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-phenanthridinyl radical, ora 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-phenanthridinyl-(C₁-C₆)-alkylradical, where the (C₁-C₆)-alkyl radical can be unsubstituted or mono-or polysubstituted by the same or different substituents from the groupof hydrogen, (C₁-C₆)-alkyl, halogen or oxo (═O), and the 1-, 2-, 3-, 4-,5-, 6-, 7-, 8- or 9-phenanthridinyl radical can be unsubstituted ormono- to octasubstituted by the same or different substituents from thegroup of (C₁-C6)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy,(C₆-C₁₀)-aryl-(C₁-C₆)-alkoxy, preferably benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0031] a 2-, 3-, 4-, 5- or 6-pyridyl radical where the 2-, 3-, 4-, 5- or6-pyridyl radical can be unsubstituted or mono- to tetrasubstituted bythe same or different substituents from the group of hydrogen,(C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0032] a 2-, 3-, 4-, 5- or 6-pyridinyl-(C₁-C₆)-alkyl radical, where the(C₁-C₆)-alkyl radical can be unsubstituted or mono- or polysubstitutedby the same or different substituents from the group of (C₁-C₆)-alkyl,halogen or oxo (═O), and the 2-, 3-, 4-, 5- or 6-pyridinyl radical canbe unsubstituted or mono- to tetrasubstituted by the same or differentsubstituents from the group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro,amino, mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0033] a 2-, 3-, 4- or 5-thienyl radical, or a 2-, 3-, 4- or5-thienyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radical can beunsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 2-, 3-, 4- or 5-thienyl radical can be unsubstituted or mono- totrisubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0034] a 2-, 4-, or 5-thiazolyl radical, or a 2-, 4-, or5-thiazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radical canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 2-, 4-, or 5-thiazolyl radical can be unsubstituted or mono- ordisubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0035] a 3-, 4-, or 5-isothiazolyl radical, or a 3-, 4-, or5-isothiazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radicalcan be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 3-, 4-, or 5-isothiazolyl radical can be unsubstituted ormono- or disubstituted by the same or different substituents from thegroup of hydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino,mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0036] a 2-, 4-, 5-, 6-, or 7-benzothiazolyl radical, or a 2-, 4-, 5-,6-, or 7-benzothiazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 2-, 4-, 5-, 6-, or 7-benzothiazolyl radical can beunsubstituted or mono- to tetrasubstituted by the same or differentsubstituents from the group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro,amino, mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0037] a 1-, 2-, 4-, or 5-imidazolyl radical, or a 1-, 2-, 4-, or5-imidazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radical canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 1-, 2-, 4-, or 5-imidazolyl radical can be unsubstituted or mono- totrisubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0038] a 1-, 3-, 4-, or 5-pyrazolyl radical, or a 1-, 3-, 4- or5-pyrazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radical canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 1-, 3-, 4- or 5-pyrazolyl radical can be unsubstituted or mono- totrisubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0039] a 1-, 2-, 3-, 4-, or 5-pyrrolyl radical, or a 1-, 2-, 3-, 4-, or5-pyrrolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radical can beunsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 1-, 2-, 3-, 4- or 5-pyrrolyl radical can be unsubstituted or mono-to tetrasubstituted by the same or different substituents from the groupof hydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino,mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0040] a 1-, 3-, or 5-[1.2.4]-triazolyl radical, or a 1-, 3-, or5-[1.2.4]-triazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of hydrogen, (C₁-C₆)-alkyl,halogen or oxo (═O), and the 1-, 3-, or 5-[1.2.4]-triazolyl radical canbe unsubstituted or mono- or disubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen, nitro, amino,mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0041] a 1-, 4-, or 5-[1.2.3]-triazolyl radical, or a 1-, 4-, or5-[1.2.3]-triazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 1-, 4-, or 5-[1.2.3]-triazolyl radical can beunsubstituted or mono- or disubstituted by the same or differentsubstituents from the group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro,amino, mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0042] a 1- or 5-[1H]-tetrazolyl radical, or a 1-, or5-[1H]-tetrazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radicalcan be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 1-, or 5-[1H]-tetrazolyl radical can be unsubstituted orsubstituted by hydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino,mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0043] a 2- or 5-[2H]-tetrazoyl radical, or a 2- or5-[2H]-tetrazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radicalcan be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 2- or 5-[2H]-tetrazolyl radical can be unsubstituted orsubstituted by hydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino,mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0044] a 2-, 4-, or 6-[1.3.5]-triazinyl radical, or a 2-, 4-, or6-[1.3.5]-triazinyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of hydrogen, (C₁-C₆)-alkyl,halogen or oxo (═O), and the 2-, 4-, or 6-[1.3.5]-triazinyl radical canbe unsubstituted or mono- or disubstituted by the same or differentsubstituents from the group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro,amino, mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0045] a 2-, 4-, or 5-oxazolyl radical, or a 2-, 4-, or5-oxazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radical can beunsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 2-, 4-, or 5-oxazolyl radical can be unsubstituted or mono- ordisubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0046] a 3-, 4-, or 5-isoxazolyl radical, or a 3-, 4-, or5-isoxazolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkyl radical canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of (C₁-C₆)-alkyl, halogen or oxo (═O), andthe 3-, 4-, or 5-isoxazolyl radical can be unsubstituted or mono- ordisubstituted by the same or different substituents from the group ofhydrogen, (C₁-C₆)-alkyl, halogen, nitro, amino, mono-(C₁-C₆)-alkylamino,di-(C₁-C₆)-alkylamino, hydroxyl, (C₁-C₆)-alkoxy, benzyloxy, carboxyl,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino or (C₁-C₆)-alkylwhich is mono- or polysubstituted by fluorine, preferablytrifluoromethyl, (C₆-C₁₀)-aryl and (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl;

[0047] a 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl radical, or a 1-, 2-, 3-,4-, 5-,6- or 7-indolyl-(C₁-C₆)-alkyl radical, where the (C₁-C₆)-alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of (C₁-C₆)-alkyl, halogen or oxo(═O), and the 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl radical can beunsubstituted or mono- to hexasubstituted by the same or differentsubstituents from the group of hydrogen, (C₁-C₆)-alkyl, halogen, nitro,amino, mono-(C₁-C₆)-alkylamino, di-(C₁-C₆)-alkylamino, hydroxyl,(C₁-C₆)-alkoxy, benzyloxy, carboxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino or (C₁ -C₆)-alkyl which is mono- orpolysubstituted by fluorine, preferably trifluoromethyl, (C₆-C₁₀)-aryland (C₆-C₁₀)-aryl-(C₁-C₆)-alkyl and the isomers, in particulartautomers, diastereomers and enantiomers, and the pharmaceuticallyacceptable salts, in particular acid addition salts, thereof.

[0048] According to a further embodiment, quinoline derivatives of theformula (1) are provided which are characterized in that R, R₁, R₂, R₃,X, Z, P, Q, n and m have the meanings given above and R₄ representsphenyl which is unsubstituted or substituted by one to five the same ordifferent (C₁-C₆)-alkoxy groups, where adjacent oxygen atoms may also belinked by (C₁-C₂)-alkylene groups.

[0049] According to a further embodiment, quinoline derivatives of theformula (1) are provided which are characterized in that R, R₁, R₂, R₃,X, Z, P, Q, n and m have the meanings given above and R₄ represents3,5-dimethoxyphenyl.

[0050] According to a further embodiment, quinoline derivatives of theformula (1) are provided which are characterized in that R₄ has themeanings given above, R, R₁, R₂, R₃ each represent a hydrogen atom, Zrepresents an oxygen atom and X represents a nitrogen atom, P and Q eachrepresent two hydrogen atoms (i.e. —CH2—), m is zero and n is theinteger 2.

[0051] According to a further embodiment, quinoline derivatives of theformula (1) are provided which are characterized in that R, R₁, R₂, R₃each represent a hydrogen atom, Z represents an oxygen atom, Xrepresents a nitrogen atom, P and Q each represent two hydrogen atoms(i.e. —CH2—), m is zero, n represents the integer 2 and R₄ represents a3,5-dimethoxyphenyl radical.

[0052] According to a further aspect of the invention, a process forpreparing quinoline derivatives of the formula (1) is provided which ischaracterized in that a quinoline carboxylic acid of the formula (2)

[0053] in which R, R1, R2, R3 have the meanings given above, Z denotesan oxygen or sulfur atom and Y represents a leaving group such ashalogen, hydroxyl, (C1-C6)-alkoxy, preferably methoxy or ethoxy,—O-tosyl, —O—mesyl or imidazolyl, is reacted with an amine of theformula (3)

[0054] in which R4, X, P, Q, m and n are as defined above, using, ifappropriate, diluents and auxiliaries, and the desired quinolinederivatives are formed.

[0055] Synthesis Route

[0056] The compounds of the formula 1 can be obtained according toScheme 1 below:

[0057] The starting materials (2) and (3) are either commerciallyavailable or can be prepared by procedures known per se. The startingmaterials (2) and (3) are useful intermediates for preparing thequinoline derivatives of the formula (1) according to the invention.

[0058] The solvents and auxiliaries to be used, if appropriate, and thereaction parameters to be used, such as reaction temperature andreaction time, are known to the person skilled in the art owing to hisexpert knowledge.

[0059] The quinoline derivatives of the formula (1) according to theinvention are suitable as medicaments, in particular as antitumoragents, for treating mammals, in particular man, but also domesticanimals such as horses, cattle, dogs, cats, hares, sheep, poultry andthe like.

[0060] According to a further aspect of the invention, a method forcontrolling tumors in mammals, in particular man, is provided which ischaracterized in that at least one quinoline derivative of the formula(1) is administered to a mammal in an amount effective for the treatmentof the tumor. The therapeutically effective dose of the quinolinederivative according to the invention in question which is to beadministered for the treatment depends inter alia on the nature and thestage of the oncosis, the age and the sex of the patient, the type ofadministration and the duration of the treatment. Administration cantake place orally, rectally, buccally (for example sublingually),parenterally (for example subcutaneously, intramuscularly, intradermallyor intravenously), topically or transdermally.

[0061] According to a further aspect of the invention, medicaments forthe treatment of tumors are provided which are characterized in thatthey comprise, as active ingredient, at least one quinoline derivativeaccording to any of Claims 1 to 4 or a pharmaceutically acceptable saltthereof, if appropriate together with customary pharmaceuticallyacceptable auxiliaries, additives and carriers. These can be solid,semisolid, liquid or aerosol preparations. Suitable solid preparationsare, for example, capsules, powders, granules, tablets. Suitablesemisolid preparations are, for example, ointments, creams, gels,pastes, suspensions, oil-in-water and water-in-oil emulsions. Suitableliquid preparations are, for example, sterile aqueous preparations forparenteral administration which are isotonic with the blood of thepatient.

[0062] The invention is to be illustrated in more detail by the examplebelow, without being restricted to the example.

1-(3,5-dimethoxyphenyl)-4-(4-quinolyl-carbonyl)piperazine

[0063] 2 g (11.5 mmol) of quinoline-4-carboxylic acid were suspended in80 ml of DMF. With stirring, 1.74 g (17.2 mmol) of N-methylmorpholineand then a solution of 8.95 g (17.2 mmol) of Py-BOP(1-benzotriazolyltripyrrolidinophosphonium hexafluorophosphate) and 2.56g (11.5 mmol) of 1-(3,5-dimethoxyphenyl)piperazine in 25 ml of DMF wereadded to this mixture. The mixture was stirred at RT for 12 h, the DMFwas distilled off under reduced pressure and the residue was purified ona silica gel column (Kieselgel 60, from Merck AG, Darmstadt) using themobile phase dichloromethane/methanol/25 percent ammonia (90:10:1v/v/v).

[0064] Yield: 3.4 g (78.3% of theory) m.p.: 146-148° C. TABLE 8 NewChinolyl-Derivatives with antitumoral activity m/e Ex. R R₁ R₂ R₃ X Z nm P Q R₄ Code-Nr. (M + H) 1 H H H H N O 2 0 H₂ H₂ 24203 378 2 H H H H NO 2 0 H₂ H₂ 43589 378 HCl- Salz 3 2-(4-chloro = H 6-CH₃ 7-Cl N O 2 0 H₂H₂ 68780 537 phenyl) 4 2-CH₃ 3-OH H H N O 2 0 H₂ H₂ 68675 408 52-(3.4-dimeth = H H 7-CH₃ N O 2 0 H₂ H₂ 68823 528 oxyphenyl)

We claim:
 1. A quinoline derivatives according to the formula 1

in which R, R₁, R₂, R₃ can be attached to any of the quinoline carbonatoms C₂ to C₈, are the same or different and independently of oneanother denote hydrogen, straight-chain or branched C₁₋₈ alkyl,hydroxyl, C₃₋₇ cycloalkyl, straight-chain or branched C₁₋₈alkylcarbonyl, straight-chain or branched C₁₋₈ alkoxy, halogen,aryl-C₁₋₈ alkoxy, nitro, amino, mono-C₁₋₄ alkylamino, di-C₁₋₄alkylamino, C₁₋₈ alkoxycarbonylamino, C₁₋₆ alkoxycarbonylamino-C₁₋₈alkyl, cyano, straight-chain or branched cyano-(C₁-C₆)-alkyl, carboxyl,C₁₋₈ alkoxycarbonyl, C₁₋₄ alkyl which is substituted by one or morefluorine atoms, carboxy-C₁₋₈ alkyl or C₁₋₈ alkoxycarbonyl-C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, straight-chain or branched cyano-C₁₋₆ alkyl,aryl, where the aryl radical can be unsubstituted or mono- orpolysubstituted by the same or different substituents from the group ofhalogen, straight-chain or branched C₁₋₈ alkyl, C₃₋₇ cycloalkyl,carboxyl, straight-chain or branched C₁₋₈ alkoxycarbonyl, bytrifluoromethyl, hydroxyl, straight-chain or branched C₁₋₈ alkoxy,benzyloxy, nitro, amino, mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino,cyano, straight-chain or branched cyano-C₁₋₆ alkyl, where R and R₁ or R₂and R₃ can form a fused aromatic 6-membered ring with the quinoline ringforming an acridine ring which can be substituted at any C atom ringposition by the radicals R, R₁, R₂ and R₃ having the meanings mentionedabove; Z is oxygen or sulfur, where the radical

 substituted on the quinoline heterocycle can be attached to C atomsC₂₋₈ of the quinoline ring; X is nitrogen or C-R₅, where R₅ is hydrogenor C₁₋₆ alkyl; n,m are independently of one another a cardinal numberbetween 0 and 3, with the proviso that when n is 0, X is a CR₅R₆ groupwherein R₅ and R₆ are independently of one another hydrogen or C₁₋₆alkyl, and that the nitrogen atom adjacent to the C═Z group issubstituted by a hydrogen atom or a C₁₋₆ alkyl group; R₄ is astraight-chain or branched C₁₋₂₀ alkyl radical which can be saturated orunsaturated, with one to three double and/or triple bonds, and which canbe unsubstituted or can optionally be substituted at the same ordifferent C atoms by one, two or more aryl, heteroaryl, halogen, cyano,C═NH (NH₂), C₁₋₆ alkoxycarbonylamino, C₁₋₆ alkoxy, amino, mono-C₁₋₄alkylamino or di-C₁₋₄ alkylamino; C₁₋₄ alkoxy carbonyl, a C₆₋₁₄ arylradical, C₆₋₁₄ aryl-C₁₋₄ alkyl radical, or a a C₂₋₁₀ heteroaryl or C₂₋₁₀heteroaryl-C₁₋₄ alkyl radical which contains one or more heteroatoms N,O and S, where the C₁₋₄ alkyl radical can be unsubstituted or mono- orpolysubstituted by the same or different substituents from the group ofC₁₋₆ alkyl, halogen or oxo (═O), and where the C₆₋₁₄ aryl or C₂₋₁₀heteroaryl radical can be unsubstituted or mono- or polysubstituted bythe same or different substituents from the group of straight-chain orbranched C₁₋₈ alkyl, C₃₋₇ cycloalkyl, halogen, cyano, C₁₋₆alkoxycarbonylamino, C₁₋₆ alkoxy, carboxyl, C₁₋₈ alkoxycarbonyl,straight-chain or branched C₁₋₆ alkyl which is substituted by one ormore fluorine atoms, hydroxyl, straight-chain or branched C₁₋₈ alkoxy,where adjacent oxygen atoms may also be linked by C₁₋₂ alkylene groups,benzyloxy, nitro, amino, mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, aryl,which can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of straight-chain or branched C₁₋₈alkyl, C₃₋₇ cycloalkyl, carboxyl, straight-chain or branched C₁₋₈alkoxycarbonyl, trifluoromethyl, hydroxyl, straight-chain or branchedC₁₋₈ alkoxy, benzyloxy, nitro, amino, mono-C₁₋₄ alkylamino, di-C₁₋₄alkylamino, cyano, straight-chain or branched cyano-C₁₋₆ alkyl; andtheir structural isomers and stereoisomers, particularly tautomers,diastereomers and enantiomers, and their pharmaceutically acceptablesalts.
 2. The quinoline derivative of claim 1, wherein in R, R₁, R₂, andR₃, said C₁₋₈ alkylcarbonyl is acetyl, said C₁₋₈ alkoxy is benzyloxy orphenylethoxy, said fluorine atoms are trifluoromethyl, said C₂₋₆ alkenylis allyl, said C₂₋₆ alkynyl is ethynyl or propargyl, said cyano-C₁₋₆alkyl is cyanomethyl, said C₁₋₈ alkoxy-carbonyl is tert-butoxycarbonyl,and said C₁₋₈ alkoxy is methoxy or ethoxy, and in R₄ said fluorine atomsare trifluoromethyl, said C₁₋₈ alkoxy is methoxy or ethoxy, and saidC₁₋₂ alkylene group is a methylene group.
 3. The quinoline derivative offormula 1 of claim 1, wherein R, R1, R2, R3, X, Z, P, Q, n and m havethe meanings given in claim 1 R4 is a straight-chain or branched C₁₋₂₀alkyl radical which can be saturated or unsaturated, with one to threedouble and/or triple bonds, and which can be unsubstituted or optionallysubstituted on the same or different C atoms by one, two or more aryl,heteroaryl, halogen, C₁₋₆ alkoxy, amino, mono- C₁₋₄ alkylamino ordi-C₁₋₄ alkylamino; a phenyl ring or a naphthyl ring, each of which canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of straight-chain or branched C₁₋₈ alkyl,C₃₋₇ cycloalkyl, halogen, cyano, C₁₋₆ alkoxycarbonylamino, C₁₋₆ alkoxy,carboxyl, C₁₋₈ alkoxycarbonyl, straight-chain or branched C₁₋₆ alkylwhich is substituted by one or more fluorine atoms, hydroxyl,straight-chain or branched C₁₋₈ alkoxy, benzyloxy, nitro, amino,mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, aryl, which can beunsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of straight-chain or branched C₁₋₈ alkyl,C₃₋₇ cycloalkyl, carboxyl, straight-chain or branched C₁₋₈alkoxycarbonyl, by trifluoromethyl, hydroxyl, straight-chain or branchedC₁₋₈ alkoxy, benzyloxy, nitro, amino, mono-C₁₋₄ alkylamino, di-C₁₋₄alkylamino, cyano, straight-chain or branched cyano-C₁₋₆ alkyl; a 2-,4-, 5- or 6-pyrimidinyl radical, or a 2-, 4-, 5- or 6-pyrimidinyl-C₁₋₄alkyl radical, wherein the C₁₋₄ alkyl radical can be unsubstituted ormono- or polysubstituted by the same or different substituents from thegroup of C₁₋₆ alkyl, halogen or oxo (═O), and the 2-, 4-, 5- or6-pyrimidinyl radical can be unsubstituted or mono- or up totrisubstituted by the same or different substituents from the group ofhydrogen, or Y wherein Y is a C₁₋₆ alkyl, halogen, nitro, amino,mono-C₁₋₆ alkylamino, di-C₁₋₆ alkylamino, hydroxyl, C₁₋₆ alkoxy,benzyloxy, carboxyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ alkoxycarbonylamino orC₁₋₆ alkyl which is mono- or polysubstituted by fluorine, C₆₋₁₀ aryl andC₆₋₁₀ aryl-C₁₋₆ alkyl; a 3-, 4-, 5- or 6-pyridazinyl radical, or a 3-,4-, 5- or 6-pridazinyl-C₁₋₄ alkyl radical, wherein the C₁₋₄ alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of C₁₋₆ alkyl, halogen or oxo(═O), and the 3-, 4-, 5- or 6-pyridazinyl radical can be unsubstitutedor mono- or up to trisubstituted by the same or different substituentsfrom the group of hydrogen, or Y; a 2-, 3-, 5- or 6-pyrazinyl radical,or a 2-, 3-, 5- or 6-pyrazinyl-C₁₋₄ alkyl radical, wherein the C₁₋₄alkyl radical can be unsubstituted or mono- or polysubstituted by thesame or different substituents from the group of C₁₋₆ alkyl, halogen oroxo (═O), and the 2-, 3-, 5- or 6-pyrazinyl radical can be unsubstitutedor mono- or up to trisubstituted by the same or different substituentsfrom the group of hydrogen, or Y; a 3-, 4-, 5-, 6-, 7-, or 8-cinnolinylradical, or a 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl-C₁₋₄ alkyl radical,wherein the C₁₋₄ alkyl radical can be unsubstituted or mono- orpolysubstituted by the same or different substituents from the group ofC₁₋₆ alkyl, halogen or oxo (═O), and the 3-, 4-, 5-, 6-, 7-, or8-cinnolinyl radical can be unsubstituted or mono- or up topentasubstituted by the same or different substituents from the group ofhydrogen, or Y; a 2-, 4-, 5-, 6-, 7-, or 8-quinazolinyl radical, or a2-, 4-, 5-, 6-, 7-, or 8-quinazolinyl-C₁₋₄ alkyl radical, wherein theC₁₋₄ alkyl radical can be unsubstituted or mono- or polysubstituted bythe same or different substituents from the group of hydrogen, C₁₋₆alkyl, halogen or oxo (═O), and the 2-, 4-, 5-, 6-, 7-, or8-quinazolinyl radical can be unsubstituted or mono- or up topentasubstituted by the same or different substituents from the group ofhydrogen, or Y; a 2-, 3-, 5-, 6-, 7-, or 8-quinoxalinyl radical, or a2-, 3-, 5-, 6-, 7-, or 8-quinoxalinyl-C₁₋₄ alkyl radical, wherein theC₁₋₄ alkyl radical can be unsubstituted or mono- or polysubstituted bythe same or different substituents from the group of C₁₋₆ alkyl, halogenor oxo (═O), and the 2-, 3-, 5-, 6-, 7-, or 8-quinoxalinyl radical canbe unsubstituted or mono- or up to pentasubstituted by the same ordifferent substituents from the group of hydrogen, or Y; a 1-, 4-, 5-,6-, 7-, or 8-phthalazinyl radical, or a 1-, 4-, 5-, 6-, 7-, or8-phthalazinyl-C₁₋₄ alkyl radical, wherein the C₁₋₄ alkyl radical can beunsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of C₁₋₆ alkyl, halogen or oxo (═O), and the1-, 4-, 5-, 6-, 7-, or 8-phthalazinyl radical can be unsubstituted ormono- or up to pentasubstituted by the same or different substituentsfrom the group of hydrogen, or Y; a 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolylradical, or a 2-, 3-, 4-, 5-, 6-, 7 or 8-quinolyl-C₁₋₄ alkyl radical,wherein the C₁₋₄ alkyl radical can be unsubstituted or mono- orpolysubstituted by the same or different substituents from the group ofC₁₋₆ alkyl, halogen or oxo (═O), and the 2-, 3-, 4-, 5-, 6-, 7- or8-quinolyl radical can be unsubstituted or mono- or up tohexasubstituted by the same or different substituents from the group ofhydrogen, or Y; a 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl radical, or a1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl-C₁₋₄ alkyl radical, wherein theC₁₋₄ alkyl radical can be unsubstituted or mono- or polysubstituted bythe same or different substituents from the group of C₁₋₆ alkyl, halogenor oxo (═O), and the 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl radical canbe unsubstituted or mono- or up to hexasubstituted by the same ordifferent substituents from the group of hydrogen, or Y; a 2-, 6-, 8- or9-[9H]-purinyl radical, or a 2-, 6-, 8- or 9-[9H]-purinyl-C₁₋₄ alkylradical, wherein the C₁₋₆ alkyl radical can be unsubstituted or mono- orpolysubstituted by the same or different substituents from the group ofC₁₋₆ alkyl, halogen or oxo (═O), and the 2-, 6-, 8- or 9-[9H]-purinylradical can be unsubstituted or mono- to trisubstituted by the same ordifferent substituents from the group of hydrogen, or Y; a 2-, 6-, 7- or8-[7H]-purinyl radical, or a 2-, 6-, 7- or 8-[7H]-purinyl-C₁₋₄ alkylradical, wherein the C₁₋₄ alkyl radical can be unsubstituted or mono- orpolysubstituted by the same or different substituents from the group ofC₁₋₆ alkyl, halogen or oxo (═O), and the 2-, 6-, 7- or 8-[7H]-purinylradical can be unsubstituted or mono- or up to trisubstituted by thesame or different substituents from the group of hydrogen, or Y; a 1-,2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl radical, or a 1-, 2-, 3-, 4-,5-, 6-, 7-, 8- or 9-acridinyl-C₁₋₄ alkyl radical, where the C₁₋₆ alkylradical can be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of C₁₋₆ alkyl, halogen or oxo(═O), and the 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl radical canbe unsubstituted or mono- to octasubstituted by the same or differentsubstituents from the group of hydrogen, or Y; a 1-, 2-, 3-, 4-, 5-, 6-,7-, 8- or 9-phenanthridinyl radical, or a 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-or 9-phenanthridinyl-C₁₋₆ alkyl radical, wherein the C₁₋₆ alkyl radicalcan be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of hydrogen, C₁₋₆ alkyl, halogenor oxo (═O), and the 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-phenanthridinylradical can be unsubstituted or mono- or up to octasubstituted by thesame or different substituents of Y; a 2-, 3-, 4-, 5- or 6-pyridylradical where the 2-, 3-, 4-, 5- or 6-pyridyl radical can beunsubstituted or mono- or up to tetrasubstituted by the same ordifferent substituents from the group of hydrogen, or Y; a 2-, 3-, 4-,5- or 6-pyridinyl-C₁₋₆ alkyl radical, wherein the C₁₋₆ alkyl radical canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of C₁₋₆ alkyl, halogen or oxo (═O), and the2-, 3-, 4-, 5- or 6-pyridinyl radical can be unsubstituted or mono- orup to tetrasubstituted by the same or different substituents from thegroup of hydrogen, or Y; a 2-, 3-, 4- or 5-thienyl radical, or a 2-, 3-,4- or 5-thienyl- C₁₋₆ alkyl radical, wherein the C₁₋₆ alkyl radical canbe unsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of C₁₋₆ alkyl, halogen or oxo (═O), and the2-, 3-, 4- or 5-thienyl radical can be unsubstituted or mono- or up totrisubstituted by the same or different substituents from the group ofhydrogen, or Y; a 2-, 4-, or 5-thiazolyl radical, or a 2-, 4-, or5-thiazolyl C₁₋₆ alkyl radical, wherein the C₁₋₆ alkyl radical can beunsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of C₁₋₆ alkyl, halogen or oxo (═O), and the2-, 4-, or 5-thiazolyl radical can be unsubstituted or mono- ordisubstituted by the same or different substituents from the group ofhydrogen, or Y; a 3-, 4-, or 5-isothiazolyl radical, or a 3-, 4-, or5-isothiazolyl-C₁₋₆ alkyl radical, wherein the C₁₋₆ alkyl radical can beunsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of C₁₋₆ alkyl, halogen or oxo (═O), and the3-, 4-, or 5-isothiazolyl radical can be unsubstituted or mono- ordisubstituted by the same or different substituents from the group ofhydrogen, or Y; a 2-, 4-, 5-, 6-, or 7-benzothiazolyl radical, or a 2-,4-, 5-, 6-, or 7-benzothiazolyl-C₁₋₆ alkyl radical, wherein the C₁₋₆alkyl radical can be unsubstituted or mono- or polysubstituted by thesame or different substituents from the group of C₁₋₆ alkyl, halogen oroxo (═O), and the 2-, 4-, 5-, 6-, or 7-benzothiazolyl radical can beunsubstituted or mono- or up to tetrasubstituted by the same ordifferent substituents from the group of hydrogen, or Y; a 1-, 2-, 4-,or 5-imidazolyl radical, or a 1-, 2-, 4-, or 5-imidazolyl-C₁₋₆ alkylradical, wherein the C₁₋₆ alkyl radical can be unsubstituted or mono- orpolysubstituted by the same or different substituents from the group ofC₁₋₆ alkyl, halogen or oxo (═O), and the 1-, 2-, 4-, or 5-imidazolylradical can be unsubstituted or mono- or up to trisubstituted by thesame or different substituents from the group of hydrogen, or Y; a 1-,3-, 4-, or 5-pyrazolyl radical, or a 1-, 3-, 4- or 5-pyrazolyl-C₁₋₆alkyl radical, wherein the C₁₋₆ alkyl radical can be unsubstituted ormono- or polysubstituted by the same or different substituents from thegroup of C₁₋₆ alkyl, halogen or oxo (═O), and the 1-, 3-, 4- or5-pyrazolyl radical can be unsubstituted or mono- or up totrisubstituted by the same or different substituents from the group ofhydrogen, or Y; a 1-, 2-, 3-, 4-, or 5-pyrrolyl radical, or a 1-, 2-,3-, 4-, or 5-pyrrolyl-C₁₋₆ alkyl radical, wherein the C₁₋₆ alkyl radicalcan be unsubstituted or mono- or polysubstituted by the same ordifferent substituents from the group of C₁₋₆ alkyl, halogen or oxo(═O), and the 1-, 2-, 3-, 4- or 5-pyrrolyl radical can be unsubstitutedor mono- or up to tetrasubstituted by the same or different substituentsfrom the group of hydrogen, or Y; a 1-, 3-, or 5-[1.2.4]-triazolylradical, or a 1-, 3-, or 5-[1.2.4]-triazolyl-C₁₋₆ alkyl radical, whereinthe C₁₋₆ alkyl radical can be unsubstituted or mono- or polysubstitutedby the same or different substituents from the group of hydrogen, C₁₋₆alkyl, halogen or oxo (═O), and the 1-, 3-, or 5-[1.2.4]-triazolylradical can be unsubstituted or mono- or disubstituted by the same ordifferent substituents from Y; a 1-, 4-, or 5-[1.2.3]-triazolyl radical,or a 1-, 4-, or 5-[1.2.3]-triazolyl-C₁₋₆ alkyl radical, wherein the C₁₋₆alkyl radical can be unsubstituted or mono- or polysubstituted by thesame or different substituents from the group of C₁₋₆ alkyl, halogen oroxo (═O), and the 1-, 4-, or 5-[1.2.3]-triazolyl radical can beunsubstituted or mono- or disubstituted by the same or differentsubstituents from the group of hydrogen, or Y; a 1- or 5-[1H]-tetrazolylradical, or a 1-, or 5-[1H]-tetrazolyl-C₁₋₆ alkyl radical, wherein theC₁₋₆ alkyl radical can be unsubstituted or mono- or polysubstituted bythe same or different substituents from the group of C₁₋₆ alkyl, halogenor oxo (═O), and the 1-, or 5-[1H]-tetrazolyl radical can beunsubstituted or substituted by hydrogen, or Y; a 2- or 5-[2H]-tetrazoylradical, or a 2- or 5-[2H]-tetrazolyl-C₁₋₆ alkyl radical, wherein theC₁₋₆ alkyl radical can be unsubstituted or mono- or polysubstituted bythe same or different substituents from the group of C₁₋₆ alkyl, halogenor oxo (═O), and the 2- or 5-[2H]-tetrazolyl radical can beunsubstituted or substituted by hydrogen, or Y; a 2-, 4-, or6-[1.3.5]-triazinyl radical, or a 2-, 4-, or 6-[1.3.5]-triazinyl-C₁₋₆alkyl radical, wherein the C₁₋₆ alkyl radical can be unsubstituted ormono- or polysubstituted by the same or different substituents from thegroup of hydrogen, C₁₋₆ alkyl, halogen or oxo (═O), and the 2-, 4-, or6-[1.3.5]-triazinyl radical can be unsubstituted or mono- ordisubstituted by the same or different substituents from the group ofhydrogen, or Y; a 2-, 4-, or 5-oxazolyl radical, or a 2-, 4-, or5-oxazolyl-C₁₋₆ alkyl radical, wherein the C₁₋₆ alkyl radical can beunsubstituted or mono- or polysubstituted by the same or differentsubstituents from the group of C₁₋₆ alkyl, halogen or oxo (═O), and the2-, 4-, or 5-oxazolyl radical can be unsubstituted or mono- ordisubstituted by the same or different substituents from the group ofhydrogen, or Y; a 3-, 4-, or 5-isoxazolyl radical, or a 3-, 4-, or5-isoxazolyl-C₁₋₆ alkyl radical, wherein the C₁₋₆ alkyl radical can beunsubstituted or mono- or poly substituted by the same or differentsubstituents from the group of C₁₋₆ alkyl, halogen or oxo (═O), and the3-, 4-, or 5-isoxazolyl radical can be unsubstituted or mono- ordisubstituted by the same or different substituents from the group ofhydrogen, or Y; a 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl radical, or a 1-,2-, 3-, 4-, 5-, 6- or 7-indolyl-C₁₋₆ alkyl radical, wherein the C₁₋₆alkyl radical can be unsubstituted or mono- or polysubstituted by thesame or different substituents from the group of C₁₋₆ alkyl, halogen oroxo (═O), and the 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl radical can beunsubstituted or mono- or up to hexasubstituted by the same or differentsubstituents from the group of hydrogen, or Y.
 4. The pyridinederivative of claim 3, wherein in R₄ said fluorine atoms aretrifluoromethyl, and said C₁₋₈ alkoxy is methoxy or ethoxy.
 5. Thequinohine derivative of claim 1, wherein R, R₁, R₂, R₃, X, Z, P, Q, nand m have the meanings given above, and R4 is phenyl which isunsubstituted or substituted by one to five the same or different C₁₋₆alkoxy groups, where adjacent oxygen atoms can also be linked by C₁₋₂alkylene groups.
 6. The quinoline derivative of claim 1, wherein R, R₁,R₂, R₃, X, Z, P, Q, n and m have the meanings given above and R₄ is3,5-dimethoxyphenyl.
 7. The quinoline derivative of claim 1, wherein R₄has the meanings given above, R, R₁, R₂, R₃ each is hydrogen, Z is anoxygen atom, X is a nitrogen atom, P and Q are each two hydrogen atomsas in —CH2—, m is zero, and n is
 2. 8. The quinoline derivative of claim1, wherein R, R₁, R₂, R₃ are each a hydrogen atom, Z is an oxygen atom,X is a nitrogen atom, P and Q each are two hydrogen atoms as in —CH2—, mis zero, n is 2, and R₄ is a 3,5-dimethoxyphenyl radical.
 9. A processfor preparing the quinoline derivative of claim 1, which comprisesreacting a quinoline carboxylic acid of formula (2)

in which R, R1, R2, R3 have the meanings given above, Z is an oxygen orsulfur atom, and Y is a leaving group with an amine of formula (3)

in which R4, X, P, Q, m and n have the meanings given above, optionallyin the presence of diluents and auxiliaries.
 10. The process of claim10, wherein said leaving group is halogen, hydroxyl, C₁₋₆ alkoxy,—O-tosyl, —O-mesyl, or imidazolyl.
 11. The process of claim 10, whereinsaid C₁₋₆ alkoxy is methoxy or ethoxy.
 12. A therapeutic method fortreating tumors in mammals, which comprises administering to a mammal inneed therefor at least one quinoline derivative of claim 1 in a tumortreatment effective dose.
 13. A medicament which comprises as activeingredient at least one quinoline derivative according of claim 1,together with conventional pharmaceutically acceptable auxiliaries,additives and carriers.
 14. The pharmaceutically acceptable acidaddition salt of the quinoline derivative of claim 1, when formed withone of the acids hydrochloric acid, hydrobromic acid, sulfuric acid,phosphoric acid, fumaric acvid, succinic acid, lactic acid, citric acid,acetic acid, tartaric acid, malic acid, maleic acid, embonic acid,malonic acid, trifluoroacetic acid, metanesulfonic acid, and sulfoaceticacid.